美國食品藥物管制局目前正在調查為何有5-15%的病人對clopidogrel無效，這被稱為clopidogrel阻抗。美國食品藥物管制局懷疑這和基因或藥物之間的交互作用有關。加拿大Sunnybrook Health Sciences Center的David Juurlink則發現這與質子幫浦阻斷劑有關。
在長達六年的急性心臟病人的研究中，發現使用clopidegrel的病人如果同時使用三種質子幫浦阻斷劑之一則再次發生心肌梗塞的機會比沒有的病人增加27%。這是因為clopidogrel需要肝臟中的細胞色素P450酵素來活化它，特別是細胞色素P450 2C19酵素。而這是很普遍且完全可以避免的藥物交互作用。
這三個藥物分別是omeprazole (Losec, Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex)。而pantoprazole (Protonix) 則沒有發現這個問題。
質子幫浦阻斷劑是一種強力的制酸劑，可以有效的減少消化性潰瘍及治療胃食道逆流，因clopidogrel有如阿司匹靈般預防血栓形成的效果且不傷胃，用於預防心肌梗塞的再次發生、心導管支架放置後預防支架的急慢性栓塞、非Q波的急性心肌梗塞、以及心導管手術前使用以減少手術併發症有不錯的效果。但因有不少病人是因服用阿司匹靈產生腸胃不適甚至潰瘍才用，目前健保規定也是必需有阿司匹靈過敏或有胃鏡證實有因阿司匹靈引起的消化性潰瘍才能處方，此時醫師為了治療潰瘍常開質子幫浦阻斷劑，這時病人已停用阿司匹靈，而如果處方時用了這三種質子幫浦阻斷劑則會使clopidogrel無效，病人等於完全沒有抗血小板的藥物保護，再次心肌梗塞的機會因此大幅增加。該研究中未提及的esomeprazole (Nexium) 因其代謝也主要由2C19酵素進行，因此很可能也會導致clopidogrel無效。
參考：
在長達六年的急性心臟病人的研究中，發現使用clopidegrel的病人如果同時使用三種質子幫浦阻斷劑之一則再次發生心肌梗塞的機會比沒有的病人增加27%。這是因為clopidogrel需要肝臟中的細胞色素P450酵素來活化它，特別是細胞色素P450 2C19酵素。而這是很普遍且完全可以避免的藥物交互作用。
這三個藥物分別是omeprazole (Losec, Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex)。而pantoprazole (Protonix) 則沒有發現這個問題。
質子幫浦阻斷劑是一種強力的制酸劑，可以有效的減少消化性潰瘍及治療胃食道逆流，因clopidogrel有如阿司匹靈般預防血栓形成的效果且不傷胃，用於預防心肌梗塞的再次發生、心導管支架放置後預防支架的急慢性栓塞、非Q波的急性心肌梗塞、以及心導管手術前使用以減少手術併發症有不錯的效果。但因有不少病人是因服用阿司匹靈產生腸胃不適甚至潰瘍才用，目前健保規定也是必需有阿司匹靈過敏或有胃鏡證實有因阿司匹靈引起的消化性潰瘍才能處方，此時醫師為了治療潰瘍常開質子幫浦阻斷劑，這時病人已停用阿司匹靈，而如果處方時用了這三種質子幫浦阻斷劑則會使clopidogrel無效，病人等於完全沒有抗血小板的藥物保護，再次心肌梗塞的機會因此大幅增加。該研究中未提及的esomeprazole (Nexium) 因其代謝也主要由2C19酵素進行，因此很可能也會導致clopidogrel無效。
參考：
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Clopidogrel and Proton-Pump Inhibitors
Risk for adverse cardiac events was elevated in patients taking both medications.
Prior biochemical studies have suggested that proton-pump inhibitors (PPIs) reduce the inhibitory effect of clopidogrel on platelet aggregation. A recent FDA review raised concerns about this issue, but data were insufficient to make a specific recommendation.
In this study, a Veterans Affairs database was used to retrospectively assess this interaction clinically in 8205 patients discharged with acute coronary syndromes (ACS); 5244 (64%) were taking both clopidogrel and a PPI, and the rest were taking clopidogrel alone. Medication use was assessed by pharmacy prescription data.At a mean follow-up of roughly 18 months, death or rehospitalization for ACS had occurred in 1561 patients (30%) taking both medications and 615 (21%) of patients taking only clopidogrel. In analyses adjusted for about 25 demographic and clinical variables, risk for death or rehospitalization was roughly 25% higher in patients taking both medications (86% higher for recurrent ACS, 49% higher for revascularization procedures, but no difference for death alone).
Comment:
As with any retrospective analysis, there are confounders for which statistical adjustment might not be fully adequate, so prospective clinical trials are needed to confirm this result. However, based on plausible biological mechanisms (e.g., inhibition by PPIs of the cytochrome P450 enzyme system responsible for the active metabolite of clopidogrel), clinicians should be more parsimonious in their use of PPIs for specific indications, rather than using them for routine prophylaxis, as is often done.
—
Thomas L. Schwenk, MDPublished in Journal Watch General Medicine March 12, 2009
Citation(s): Ho PM et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009 Mar 4; 301:937.
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